Endo-pemhydro-x



United States Patent 3,124,595 N (PSEUDOTHIGURQNHUM LQWER ALKYL)- ENDO-PERHYDRG-dfl-MET OHSOENDGUE James W. Bolger, Canoga Park, Caliih, assignor to or Laboratories, linc., Northridge, Calif., a corporation of Deiaware No Drawing. Filed July 27, 1962, Ser. No. 213,031

2 Claims. (Cl. 26tl319) radical.

The tangible embodiments of this invention possess the inherent general physical characteristics of being, in the form of their acid addition salts, white crystalline solids. Spectral data reveal no unsaturation except as present in the NH portion of peudothiouronium radical. The aforementioned physical characteristics, taken together with the nature of the starting materials and the mode of synthesis, positively confirm the structure of the compounds sought to be patented.

The tangible embodiments of this invention possess the inherent applied use characteristics of having pharmacological activity as anti-hypertensive agents, local anesthetic agents and as agents for prolonging the effects of pharmacologically active barbituric acid derivatives as determined by recognized and accepted pharmacological test procedures.

The manner and process of making and using the invention will now be generally described so as to enable a person skilled in the art of chemistry to make and use the same as follows:

The starting materials for the compounds of this invention, N-haloalkyl-endo-perhydro 4,7 methanoisoindoles, are prepared according to the method described in my application entitled N-(Haloalkyl)-Endo-Perhydro- 4,7-Methanoisoindoles, Serial No. 213,050 filed July 27, 1962. i

The preparation of the tangible embodiments of this invention is illustrated as follows:

where A is lower alkylene and X is a halogen.

3,124,595 Patented Mar. 10, 1964 The reaction depicted hereinabove is carried out by treating the starting material with thiourea in the presence of an inert solvent such as ethanol or propanol at reflux temperature.

The tangible embodiments of this invention can, if desired, be converted into their non-toxic pharmaceutically acceptable acid addition or quaternary ammonium salts by conventional procedures. Typical acid addition salts include the hydrochloride, hydrobromide, citrate, maleate, sulfate, nitrate and the like. Typical quaternary ammonium salts are those formed with such alkyl halides as methyl iodide, n-hexyl bromide and the like. Such salts are the full equivalents of the free bases and are included within the scope of this invention.

The tangible embodiments of this invention, either as the free base or in the form of a non-toxic pharmaceutically acceptable acid addition or quaternary ammonium salt, may be combined with conventional pharmaceutical diluents and carriers to form such dosage forms as tablets, capsules, solutions, suspensions, suppositories and the like.

The best mode contemplated by the inventor for carrying out this invention will now be set forth as follows:

EXAMPLE N (2 '-Pseud0thiouronium-Ethyl -End0-Perhya'r0- 4,7-Methan0is0ind0le Chloride Hydrochloride N (2 chloroethyl) endo perhydro 4,7 methanoisoindole hydrochloride (5 g., 0. 0212 mole) is mixed with thiourea (1.61 g., 0.0212 mole). Isopropanol (30 m1.) is added and the mixture is refluxed for three hours. Upon cooling the solution white crystals are obtained. Ethylacetate is added to complete crystallization. The crude product obtained in recrystallized from ethanol/ ether (anhydrous). Yield 5.6 g. of white crystals, MP. 245 C.

Analysis.-Calculated for C H N Cl S: C, 46.15%; H, 742%; C1, 22.71%. Found: C, 46.07%; H, 7.23%; Cl, 22.62%.

The subject matter which the applicant regards as his invention is particularly pointed out and distinctly claimed as follows:

1. A compound of the formula where A is lower alkylene.

2. N (2' pseudothiouronium ethyl) endo perhydro-4,7-methanoisoindole.

No references cited. 

1. A COMPOUND OF THE FORMULA 